Structural Insights into IP3R Function.
Structural Insights into IP3R Function.
复制标题
IP3R 功能的结构见解。
DOI：
10.1007/978-3-319-55858-5_6
复制
发表时间：
2017
影响因子：
--
通讯作者：
Fan,Guizhen
中科院分区：
文献类型：
--
作者：
Serysheva,IrinaI;Baker,MariahR;Fan,Guizhen
肌醇1，4，5-三磷酸受体（IP 3R）是广泛表达于几乎所有真核细胞内质网上的胞内配体门控Ca 2+通道。这些通道响应于信号传导分子IP 3的激活而介导Ca 2+从细胞内储存的释放，所述信号传导分子IP 3用于将细胞接收的不同信号（例如来自激素、神经递质、生长因子和肥大刺激）传递到细胞内的各种信号传导途径。因此，IP 3R通道可以被概念化为高度动态的支架膜蛋白复合物，其中配体的结合可以改变支架结构，导致细胞Ca 2+信号，其指导显著不同的细胞作用。虽然在生理和生化研究中得到了广泛的表征，但IP 3Rs如何响应于多样化的细胞外和细胞内刺激而产生高度受控的Ca 2+信号的详细机制仍然未知，并且需要通道分子结构的高分辨率知识。最近，单粒子电子低温显微镜（cryo-EM）已经产生了期待已久的近原子分辨率结构的整个全长1型IP 3R。这种结构提供了重要的见解配体介导的激活和调节IP 3R的分子基础。在本章中，我们评估现有的信息和研究进展的结构IP 3R通道，试图阐明其功能。
Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed intracellular ligand-gated Ca2+channels present on the endoplasmic reticulum of virtually all eukaryotic cells. These channels mediate the Ca2+release from intracellular stores in response to activation by the signaling molecule IP3, which functions to transmit diverse signals received by the cell,e.g.from hormones, neurotransmitters, growth factors and hypertrophic stimuli, to various signaling pathways within the cell. Thus, IP3R channels can be conceptualized as highly dynamic scaffold membrane protein complexes, where binding of ligands can change the scaffold structure leading to cellular Ca2+signals that direct markedly different cellular actions. Although extensively characterized in physiological and biochemical studies, the detailed mechanisms of how IP3Rs produce highly controlled Ca2+signals in response to diversified extra- and intracellular stimuli remains unknown and requires high-resolution knowledge of channel molecular architecture. Recently, single-particle electron cryomicroscopy (cryo-EM) has yielded a long-awaited near-atomic resolution structure of the entire full-length type 1 IP3R. This structure provides important insights into the molecular underpinnings of ligand-mediated activation and regulation of IP3R. In this chapter, we evaluate available information and research progress on the structure of IP3R channel in an attempt to shed light on its function.